Trends in gynecological cancer incidence, mortality, and survival among elderly women: A SEER study

Abstract Objectives This paper aims to comprehensively analyze trends in gynecological cancers among elderly women in the United States from 1975 to 2020. Methods Surveillance, Epidemiology, and End Results (SEER) population data were utilized for the analysis. Annual Percentage Change (APC) and Average APC were estimated using join‐point regression to assess trends in mortality rates. Results The study reveals an increasing pattern of incidence and mortality in all gynaecological cancer sites except cervical cancer among elderly. The incidence of cervical cancer decreased from 1975 to 2007 and then increased, whereas cancer‐specific mortality decreased from 1977 to 2020, indicating positive advancements in detection and treatment. Conclusions Despite progress in managing certain gynecological cancers, challenges persist, particularly evidenced by increasing mortality rates for cancers in other female genital organs. This underscores the necessity for sustained research efforts and targeted interventions to address these ongoing challenges effectively.


| INTRODUC TI ON
Gynecological cancers encompass cancers affecting the cervix uteri, corpus uteri, ovaries, fallopian tubes, vulva, and vagina.This category presents a significant public health challenge due to the persistent role of gynecological malignancies as a leading cause of cancer-related mortality.The global burden of cancer incidence and mortality is escalating rapidly, driven by both population growth and aging.According to GLOBOCAN report, gynecological cancers contribute to nearly 40% of all cancer cases and over 30% of all cancerrelated deaths among women worldwide. 1rvical cancer presently stands as the second most prevalent gynecological cancer, with 0.6 million new cases reported in 2020.
It ranks fourth among causes of cancer-related deaths in women, claiming approximately 342,000 lives globally. 2Ovarian cancer ranks fourth among gynecological malignancies, with approximately 313,959 new cases and 207,252 deaths in 2020.Uterine cancer is the third most diagnosed cancer in women worldwide, with an estimated 66,200 new cases and 13,030 deaths in the United States in 2023 (Siegel et al., 2023). 3Despite advancements in cancer research, the incidence of gynecological malignancies in the United States continues to rise.The factors contributing to this increase are likely multifactorial, heterogeneous, and poorly understood.
Several industrialized countries, including the United States, have witnessed an uptick in the incidence of gynecological cancers among women.A study by Knudsen et al. 4 explored trends in incidence, mortality, and survival in gynecological cancers among elderly Danish women from 1980 to 2012.They concluded that mortality rate and survival are age-dependant with significant shorter survival for the elderly.Piechocki et al. 5 reported a significant increase in ovarian and corpus uteri cancer, as well as breast cancer, and a decrease in cervical and vaginal cancer incidence in Poland.A recent study in the United States by Somasegar et al. 6 analyzed uterine cancer mortality trends over a 50-year period, emphasizing age and race.They observed a sixfold higher uterine cancer mortality rate for patients aged 70 years or older compared to those aged 50 to 59 years.
Advancing age is a major risk factor for cancer, with individuals over 65 years accounting for 60% of newly diagnosed malignancies and 70% of all cancer deaths (Berger et al., 2006). 7,8Elderly women are frequently diagnosed at later stages and experience worse outcomes than younger patients. 9,10Consequently, there may be an unmet need among older women in terms of gynecological cancer prevention and treatment. 11e objective of this study is to utilize United States Surveillance, Epidemiology, and End Results (SEER) population data to analyze trends in the incidence and mortality of gynecological cancers among elderly women between 1975 and 2020.
A detailed and comprehensive analysis of gynecological cancer trends will aid policymakers in assessing the cancer burden, establishing health service infrastructures, and allocating public health resources.

| Data sources
Retrospective data for this study were sourced from the National Cancer Institute's SEER 8 registry database (November 2022 supplement, 1975-2020).Cancer data pertaining to the female genital system, encompassing all gynecological cancer sites (cervix, corpus, ovary, vagina, vulva, fallopian tube and other female genital organs), were extracted.The analysis has focused on women aged 65 years or above, excluding cases with nonclinical reporting sources (autopsy only, death certificate, nursing/convalescent home/hospital), missing cause of death information, or zero survival months.
The variables included in the analysis comprised age at first diagnosis, year of diagnosis, cancer site, survival months, vital status, and cause of death.Gynecological cancer-specific mortality was the primary outcome, with other cause-related deaths considered as the secondary endpoint.Patient status was determined by combining SEER cause-specific death classification and SEER other cause of death classification variables.Year of mortality was obtained by adding the survival months with year of diagnosis.Program, National Cancer Institute, Bethesda, MD), was performed to identify trends. 12The number of joinpoints ranged between 0 and 3, allowing the selection of the best-fitting model with the estimated annual percentage change (APC) for each segment.The average APC (AAPC) illustrated the trend over the entire period.When no change points were found, only one APC value represented the trendline for the whole period.The detail mathematical treatment of joinpoint regression is given in the following section.

| Joinpoint regression model
Joinpoint regression analysis is being performed to identify the period in which any significant changes on cancer-specific mortality rates for cervix, corpus, ovary, vagina, vulva, fallopian tube, and other female genital organs during 1975 to 2020.
The APC and AAPC were proposed to summarize and compare the rate of changes of cancer-specific mortality rates that occur over the given period of time and given by: All statistical analyses were conducted using MS Excel and SPSS.
A P value <0.05 was deemed statistically significant.

| Ethical approval
As this data is available on public sources, i.e., the SEER database of the National Cancer Institute (http:// seer.cancer.gov), no ethical clearance is required for this study.

| RE SULTS
The Table 1 shows the descriptive characteristics of the study population.The present study incorporated a cohort of 112,192 women, characterized by a median age of 75 years and median (1) survival duration of 43 months after diagnosis.The racial composition of the study population was as follows: 4.6% Hispanic, 83.2% Non-Hispanic White, 5.7% Non-Hispanic Black, 5.8% Non-Hispanic Asian or Pacific Islander, 0.5% Non-Hispanic American Indian/Alaska Native, and 0.2% categorized as Non-Hispanic Unknown Race.
Over the course of 1975 to 2020, a noteworthy fourfold surge in the diagnosis of gynecological cancer cases among elderly women was observed.Uterine corpus cancers accounted for the majority, comprising 56.3% of the cases, followed by 25.1% in the ovary.
Despite this, only 23.5% of the cases resulted in survival, while a substantial 76.5% faced mortality.Of this mortality, 39.3% was attributed to cancer.From the above (Table 4) we can infer that gynecological cancers vary significantly in their survival rates.Uterine corpus cancer having a 76% survival rate, vulva cancer at 70%, and cervical cancer at 56% indicates differences in prognosis.All other types of gynecological cancers under consideration were found to have much lower 5-year survival rates (Figure 3).75 to 79 and 80 to 84 exhibit the highest cancer incidence rates. 17

The data presented in
The observed fourfold surge in gynecological cancer diagnoses among elderly women from 1975 to 2020 is a notable trend, with uterine corpus cancers constituting the majority.However, despite the prevalence of uterine corpus cancers, the survival rates remain a concern, as only 23.5% of cases result in survival, and a substantial 76.5% face mortality, with 39.3% attributed to cancer.The temporal trend analysis elucidates a remarkable increase in key indicators, including incidence, overall mortality, cancerspecific mortality, and mortality due to other causes over the study period.
The descriptive statistics underscore the evolving landscape of gynecological cancer incidence over the studied period, emphasizing the predominance of uterine corpus cancers and the critical impact on survival outcomes.The racial distribution further elucidates the diverse demographic representation within the study, shedding light on disparities that may influence cancer-related outcomes.
According to Somasegar et al., 6

Figure 1
Figure 1 depicts the temporal trend in gynecological cancer incidence and mortality among elderly women spanning the years 1975 to 2020.Strikingly, all key indicators, including incidence, overall mortality, mortality attributed to cancer specific, and mortality due to other causes, have experienced a substantial and notable increase over this time frame.

1977 to 4 .F I G U R E 2
2% in 2008 to 2020.The AAPC for uterine corpus cancer mortality rate was also found to be significant at 5.3%, indicating a notable decrease over the years.For ovarian cancer, the APC in mortality rate demonstrated a significant reduction from 36% in 1975 to 1977 to −0.5% in 2001 to 2020.The AAPC for ovarian cancer mortality rate was found to be significant at 2.8%, suggesting a sustained decrease over the study period.Moreover, the mortality rates for vaginal, vulvar, and fallopian tube cancers showed significant decreases in both APC and AAPC over the entire period under consideration, reflecting positive trends in the management of these cancers.Conversely, cancer in other female genital organs displayed a statistically significant APC of 19% during 2006 to 2020, underscoring the need for further investigation and intervention in this specific category.The comparison between Tables4 and 6highlights the diverse survival rates among gynecological cancers and their corresponding trends in mortality rates over time.Uterine corpus cancer demonstrates a relatively higher 5-year survival rate compared to vulva cancer, indicating differences in prognosis.Cervical cancer exhibits a remarkable decline in annual mortality rates, reflecting substantial progress in its management.Similarly, uterine corpus and ovarian cancers show significant reductions in mortality rates over the study period, suggesting improvements in their treatment.Conversely, other female genital organ cancers exhibit a notable increase in mortality rates, emphasizing the necessity for further investigation and intervention.Joinpoint regression analysis of trends in incidence (A), overall mortality (B), mortality due to cancer (C), and mortality due to other causes (D).TA B L E 4 5 year survival of different gynecological cancers.

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elderly women.It underscores the importance of understanding and addressing the unique challenges posed by different gynecological cancers.The trends in cancer-specific mortality rates provide additional insights, with cervical, uterine corpus, and ovarian cancers displaying significant declines over the study period.However, the rise in mortality rates for other female genital organs during 2006 to 2020 warrants attention and further investigation.These findings collectively contribute to the body of knowledge surrounding gynecological cancers among elderly women, guiding future research directions and informing targeted interventions to improve outcomes in this population.The strength of our analysis lies in the most recent available SEER population-based registry data and it also provides a detailed overview of gynecological cancer epidemiology, particularly in elderly women.It is worth noting here the limitation of our study that the registry data did not reveal the causes for change in documentation.CON CLUS ION This comprehensive analysis of gynecological cancer trends among a substantial cohort of elderly women spanning 1975 to 2020 illuminates critical insights into incidence, survival rates, and mortality patterns.The observed fourfold surge in diagnoses underscores the evolving landscape of these cancers, with uterine corpus cancers notably prevalent.Despite advancements in health care, survival rates vary significantly among different gynecological cancers, emphasizing the urgency for tailored preventive and management strategies.Encouragingly, the declining overall mortality rate and cancer-specific mortality rates for cervical, uterine corpus, and ovarian cancers signify positive strides in detection and treatment.However, the persistent challenges and increasing mortality rates for cancers in other female genital organs during the most recent period highlight the need for continued research and targeted interventions.These findings collectively contribute valuable insights to the field, guiding future efforts to enhance the understanding and management of gynecological cancers in the elderly population.
Descriptive statistics have been presented for both continuous and categorical variables.The Kaplan-Meier technique was employed to estimate the survival function.Joinpoint regression analysis, utilizing the joinpoint regression program version 4.8.0.1 (Statistical Methodology and Applications Branch, Surveillance Research

Table 5
offers a comprehensive overview of the APC and AAPC in the incidence of different gynecological cancers spanning the years 1975 to 2020.Firstly, the incidence of cervical cancer displayed a notable shift, with the APC increasing significantly from −0.8% in 1975 to 1994 to 1.6% in 2007 to 2020, The above (Table 6) elucidates the APC and AAPC in cancerspecific mortality rates for various gynecological cancers spanning the years 1975 to 2020.Beginning with cervical cancer, a remarkable decline in APC is observed, decreasing significantly from 88.9% in 1975 to 1977 to −0.6% in 1977 to 2020.The AAPC for cervical cancer mortality rate was also found to be significant at 2.2%, signifying a noteworthy sustained reduction over the entire duration.Similarly, uterine corpus cancer exhibited a substantial shift, with the APC in mortality rate dropping significantly from 72.7% in 1975 to TA B L E 3 Annual percentage changes in overall gynecological cancer incidence, mortality and cancer-specific mortality among elderly women (1975-2020).*Indicatesthat the APC and AAPC are significantly different from zero at the α = 0.05 level).

Site 5-year survival Std. Error 95% CI Lower Upper
5ur study systematically analyses the gynecological cancer among elderly women of United States for the period 1975 to 2020 using joinpoint regression model.A study byPiechocki et al. revealeda correlation between age groups and the incidence and mortality rates of each assessed cancer, underscoring the importance of considering age-specific factors in understanding and addressing cancer outcomes.5AstudybyCui et al.14examines cancer incidence and survival rates in individuals aged 55 and older in the United States, crucial in aging societies like the United States.Utilizing data from the SEER database spanning 1975 to 2019, the study finds a decreasing trend in cancer incidence but increasing survival rates among this demographic.Notably, individuals aged F I G U R E 3 Kaplan-Meier Plot for 5year survival by cancer site.TA B L E 5 APC and AAPC of incidence of different gynecological cancer, 1975 to 2020.
The analysis of gynecological cancer trends over different periods reveals significant insights into both incidence and mortality rates.The APC in incidence showed statistical significance during specific periods, emphasizing the dynamic nature of these cancers.
across age groups shed light on distinct patterns.Cervical cancer sees an increase in the 65 to 69 and 70 to 74 age brackets, while uterine corpus cancer rises significantly among women aged 85 and above.Ovarian cancer displays a decline in incidence for age groups under 79 but rises substantially in women aged 80 and above.Vaginal and vulvar cancers follow a similar pattern, with a decrease TA B L E 6 APC and AAPC of cancer-specific mortality of different gynecological cancer, 1975 to 2020.in incidence under 80 and a significant increase in those aged 80 and above.These age-specific trends underscore the importance of tailoring preventive and management strategies to different age cohorts.